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Myeloid cells contribute to the etiology of multiple sclerosis (MS), but the dynamics of myelopoiesis during disease progression is still unclear. Here the authors show, in both mouse models and clinical data, that myelopoiesis is differentially regulated via M-CSF modulation in different organs at distinct stages of MS, with diet and lifestyle being potential modifiers.

Kodali, Proietti et al. report that increased numbers of P-bodies in leukaemia cells account for sequestration and prevention of tumour-suppressive mRNAs from being translated, which could be targeted as a potential intervention in myeloid leukaemia.

A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

The ability to maintain blood stem cells (HSCs) in vitro would allow us to provide better therapies for blood diseases. Here, the authors report that polymer-organised extracellular proteins, coupled to soft environments mimicking bone marrow stiffness, allow stromal cells to maintain HSCs in vitro.

Patients who survive sepsis are at increased risk of infection owing to long-term immunosuppression that is associated with an increase in Treg cell numbers. Here the authors show expansion of the Treg cell population in sepsis mice is driven by IL-33-induced ILC2 activation of IL-10 production by macrophages.

Kwak et al. report that adherens junctions organize membrane microdomains, leading to lipid-dependent γ-secretase recruitment and size-dependent protein segregation, excluding full-length Notch receptor.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

A meta-analysis of genome-wide association study data from 77,418 individuals of East Asian ancestry with type 2 diabetes identifies novel variants associated with increased risk of type 2 diabetes.

Using single-nucleus RNA sequencing from 32 donors, researchers identified distinct astrocytic gene expression programs activated across brain regions and Alzheimer’s disease stages. They also found unique subclusters of astrocytes that appear to vary over time, highlighting the complexity of astrocytic responses in AD.

A synthetic receptor platform that enables mammalian cells to respond to soluble factors allows specific signalling networks to be precisely controlled, with a variety of therapeutic applications.

A high-resolution, global atlas of mortality of children under five years of age between 2000 and 2017 highlights subnational geographical inequalities in the distribution, rates and absolute counts of child deaths by age.

A randomized trial in patients hospitalized with COVID-19 showed no benefit and potentially increased harm associated with the use of convalescent plasma, with subgroup analyses suggesting that the antibody profile in donor plasma is critical in determining clinical outcomes.

The human reference genome does not fully reflect human genetic diversity. Here, the authors analyse 338 human genome assemblies from diverse populations to identify missing sequences, define non-reference unique insertions and construct a Human Diversity Reference.

The proteasome of Plasmodium falciparum (Pf20S) is a promising multi-stage drug target. Using CryoEM Hsu et al. report the structures of parasite and human proteasome in complex with the recently developed inhibitor TDI-8304 to gain insights into its species selectivity.

Deaths from alcohol-related liver disease have sharply increased following the Covid-19 pandemic. Here, the authors show that binge-pattern alcohol consumption, genetic factors and the presence of diabetes mellitus confer the greatest risk, allowing targeted interventions for high-risk individuals.

Selective sweeps are events in which beneficial mutations spread rapidly through a population. Here, Sugden et al. develop SWIF(r), a probabilistic classification framework for detecting and localizing selective sweeps, and apply it to genomic data from the ‡Khomani San.

FINO₂ is a small molecule that requires the endoperoxide moiety and hydroxyl group to promote ferroptosis through indirect inhibition of GPX4 enzymatic function and direct oxidation of iron, resulting in increased lipid peroxidation.

The lack of appropriate models restricts pre-clinical research for nasopharyngeal carcinoma (NPC). Here the authors report the development and characterization of NPC patient-derived xenografts (PDXs), and EBV positive NPC cell line from patient tumor, and suggest their potential use in future NPC research.

Mutations in the splicing factor RBM20 cause aggressive Dilated Cardiomyopathy. Here the authors generated RBM20 R636S mutants and knockout in human iPSC-derived cardiomyocytes. Mutant RBM20 showed different target RNA binding, altered splicing and localization to cytoplasmic processing bodies.

Long non-coding RNAs contribute to the regulation of gene expression. Crooks and colleagues profile the long non-coding RNA transcriptome during the specification and development of human lymphocytes.

Using genetic approaches and transcriptional profiling, Kallies and colleagues reveal a common program of effector CD8⁺ T cell differentiation that is regulated by the cooperation of IL-2 and IL-12 signaling and the combined activities of the transcriptional regulators Blimp-1 and T-bet.

Heart rate variability (HRV) describes the individual variation in cardiac cycle duration and is a measure of vagal control of heart rate. Here, the authors identify seventeen single-nucleotide polymorphisms associated with HRV, lending new insight into the vagal regulation of heart rhythm.

Carotid intima-media thickness (cIMT) and plaque are associated with subclinical atherosclerosis and coronary heart disease (CHD). Here, the authors identify and prioritize genetic loci for cIMT and plaque by GWAS and colocalization approaches and further demonstrate genetic correlation with CHD and stroke.

Large structural variants (SV) are understudied in human genetics research because of the difficulty to detect them in the routinely generated short-read sequencing data. Here, the authors generate optical genome maps of 154 individuals from 26 populations that allow comprehensive examination of large SVs.

The ovary surface epithelium undergoes ovulation-induced tear and remodelling. Barker and colleagues have identified Lgr5-expressing stem cells in the mouse ovary and show that they contribute to ovary organogenesis as well as participate in epithelial repair throughout life.

The next step after sequencing a genome is to figure out how the cell actually uses it as an instruction manual. A large international consortium has examined 1% of the genome for what part is transcribed, where proteins are bound, what the chromatin structure looks like, and how the sequence compares to that of other organisms.

The heart arises from distinct progenitors. Blanpain and colleagues use clonal analysis to demonstrate that early prospective cardiac progenitors, marked by Mesp1 appearing at gastrulation, are already restricted to a particular lineage and heart region.

Ligand-triggered ribosomal frameshifting allows control of the relative stoichiometry of two proteins and enables the building of logic gates from a single mRNA.

An international consortium reports the genomic sequence for ten Drosophila species, and compares them to two other previously published Drosophila species. These data are invaluable for drawing evolutionary conclusions across an entire phylogeny of species at once.

Meta-analysis of three large whole-exome sequencing datasets highlights protein-truncating and rare missense variants associated with breast cancer susceptibility.

Cardelino leverages variant information from single-cell RNA-seq data for inferring clonal tree configuration and mapping cells to their clone of origin.

Perez-Bermejo et al. performed an in-depth study on a variant in the BAG3 gene that has been previously associated with lowered incidence of heart failure and show that, in induced pluripotent stem cell-derived cardiomyocytes engineered to express such BAG3 variant, the interactome of the corresponding BAG3 protein has changed, rendering the engineered cardiomyocytes more resistant to a well-known cardiotoxic drug.

A benchtop system for protein synthesis achieves purity and potency comparable to those of marketed drugs.